Universal carrier for targeting molecules to Gb3 receptor expressing cells

Abstract

The present invention concerns an universal polypeptidic carrier for targeting directly or indirectly a molecule to Gb3 receptor expressing cells and having the following formula STxB-Z(n)-Cys, wherein: STxB is the Shiga Toxin B subunit or a functional equivalent thereof, Z is an amino-acid devoided of sulfydryl group, n being 0, 1 or a polypeptide, Cys is the amino-acid Cysteine, and the use thereof for MHC class I and MHC class II presentation of antigens.

1. A universal polypeptidic carrier for targeting directly or indirectly a molecule to Gb3 receptor expressing cells and having the following formula STxB-Z(n)-Cys, wherein:
 STxB is the Shiga Toxin B subunit or a functional equivalent thereof, 
 Z is an amino-acid devoid of a sulfhydryl group, n being 0, 1 or a polypeptide, 
 Cys is the amino-acid Cysteine, wherein said molecule is an antigen to be targeted to antigen presenting cells. 
 
     
     
       2. The universal carrier according to  claim 1  wherein n is 0. 
     
     
       3. The universal carrier according to  claim 1  or  2  wherein the molecule is covalently linked to the —S residue of the universal carrier by a —S—S—, a —S—CO—, a —S—CH 2 — or a —S—NH— linkage. 
     
     
       4. The universal carrier according to  claim 1  or  2  wherein the universal carrier is covalently linked to an oligopeptide or a polypeptide by a —S—S—, or a —S—CO—, or a —S—CH 2 — or a —S—NH— linkage, and the molecule to be targeted is operably linked to said oligopeptide or polypeptide. 
     
     
       5. The universal carrier according to  claim 4  wherein the universal carrier is covalently linked to a poly-lysine oligopeptide and the molecule to be targeted is nucleic acid or an oligo-nucleotide operably linked to the said poly-lysine moiety. 
     
     
       6. The universal carrier according to  claim 3  wherein the molecule is a cytotoxic drug or a pro-drug to be targeted to tumor cells expressing Gb3 receptors. 
     
     
       7. A universal carrier for targeting directly or indirectly a molecule to Gb3 receptor expressing cells and having the following formula STxB-Z(n)-Cys, wherein:
 STxB is the Shiga Toxin B subunit or a functional equivalent thereof, 
 Z is an amino acid devoid of a sulfhydryl group, n being 0, 1 or a polypeptide, 
 Cys is the amino acid Cysteine, wherein said molecule is selected from the group of proteins, glycoproteins, nucleic acids encoding proteins and a combination thereof. 
 
     
     
       8. A universal polypeptidic carrier for targeting directly or indirectly a molecule to Gb3 receptor expressing cells and having the following formula STxB-Z(n)-Cys, wherein:
 STxB is the Shiga Toxin B subunit, 
 Z is an amino acid devoid of a sulfhydryl group, n being 0, 1 or a polypeptide, 
 Cys is the amino acid Cysteine, wherein said molecule is selected from the group of proteins, glycoproteins, nucleic acids encoding proteins and a combination thereof. 
 
     
     
       9. A universal polypeptidic carrier for targeting directly or indirectly a molecule to Gb3 receptor expressing cells and having the following sequence: 
       
         
           
                 
               
                   (SEQ ID No; 1) 
                 
                 
               
                   COOH- 
                 
                     
                 
                   MKKTLLIAASLSFFSASALATPDCVTGKVEYTKYNDDDTFTVKVGDKELF 
                 
                     
                 
                   TNRWNLQSLLLSAQITGMTVTIKTNACHNGGGFSEVIFRC-NH 2 . 
                 
             
                
               
            
             
                
                
                
                
                
               
            
           
         
       
     
     
       10. A universal polypeptidic carrier for targeting directly or indirectly a molecule to Gb3 receptor expressing cells and having the following formula STxB-Z(n)-Cys, wherein:
 STxB is the Shiga Toxin B subunit, 
 Z is an amino acid devoid of a sulfhydryl group, n being 0, 1 or a polypeptide, 
 Cys is the amino acid Cysteine, wherein said molecule is a cytotoxic drug or a pro-drug to be targeted to tumor cells expressing Gb3 receptors. 
 
     
     
       11. A universal polypeptidic carrier for targeting directly or indirectly a molecule to Gb3 receptor expressing cells and having the following formula STxB-Z(n)-Cys, wherein:
 STxB is the Shiga Toxin B subunit or a functional equivalent thereof, 
 Z is an amino-acid devoid of a sulfhydryl group, n being 0, 1 or a polypeptide, 
 Cys is the amino-acid Cysteine, wherein the molecule is selected from the group consisting of proteins, peptides, oligopeptides, glycoproteins, glycopeptides, nucleic acids, polynucleotides, and a combination thereof.